Abnormal transmission to receptors in the central nervous system (CNS) have been implicated in wide variety of diseases, such as Parkinson's disease, psychosis, and many others. Currently, many therapies for these diseases are based upon the use of a medicament as an agonist to stimulate a receptor, or as an antagonist to block a receptor. For example, the treatment of psychosis has been associated with medicament antagonism with dopaminergic receptors.
The ability of a medicament to be effective in vivo to effectively interact with CNS receptors depends upon many factors, including the binding affinity of the medicament for a receptor, the medicaments ability to cross the blood-brain barrier, and the selectivity of the medicament for a targeted receptor. For example, to treat psychotic activity a medicament would be a selective antagonist for the D4 dopamine receptor.
To date, many medicaments with good binding affinities for a particular CNS receptor also bind to non-targeted receptors, often resulting in undesirable side-effects. For example, common side-effects of anti-psychotic drugs include extrapyramidal side-effects. Similarly, some atypical anti-psychotic drugs, such as clozapine which is selective for the D4 receptor, have not exhibited extrapyramidal side-effects but have had severe effects upon the patient's white blood cells, such as agranulocytosis.
Consequently, compositions are needed that can cross the blood-brain barrier to act in vivo and selectively target a CNS receptor without causing severe extrapyramidal side-effects, agranulocytosis or other side-effects associated with current medicaments.